Is late-life depression associated with alzheimer's disease? evidence from epidemiological, neuropsychological, and neuroimaging perspectives

In 2021, the FDA approved Aducanumab (Aduhelm™), an anti-amyloid antibody intravenous (IV) infusion therapy approved for Alzheimer's disease (AD) that is the first treatment shown to ameliorate neuropathological changes due to AD in the brain. It is well-established that depression increases the risk of future cognitive decline and dementia, but whether depression is specifically associated with AD is unclear, because many of the earlier epidemiological studies employed a relatively short interval (< 5 years) between observation of depression and AD diagnosis. Since neuropathological changes in the brain due to AD may occur years prior to onset of clinical memory symptoms and AD diagnosis, depression that begins late in life may thus represent a non-cognitive prodromal feature of AD. Moreover, the association between depression in older adults and AD biomarkers is also unclear, with some studies suggesting that amyloid-beta, one of the main neuropathological hallmarks of AD, may be reduced in older adults with depression. With the availability of a disease-altering treatment for AD and knowledge that the neuropathological process for AD begins years before onset of clinical memory symptoms, a logical next step in the near future will be to examine whether anti-amyloid therapies can prevent development of AD in high-risk populations. Thus, it is timely to clarify the relationship between depression and dementia. Specifically, is depression an independent risk factor for AD, or is depression associated with dementia more generally? What is the evidence for a distinct form of dementia subtype due to depression?